Staphylococcus aureus is a major pathogen causing serious infections, including large outbreaks, among military personnel. Currently, antibiotic-resistant strains of this organism, methicillin-resistant S. aureus (MRSA), are increasing in prevalence among service members, causing large outbreaks in training facilities and during deployment. The unique environment and activities associated with military training and deployment leave the military community at increased risk for the spread of S. aureus among its members. These infections are easily spread among service members, as well as among their families, affiliated personnel, and the civilian community, and are a significant cause of morbidity and mortality. Thus, our proposed area of study, S. aureus infections, is directly relevant to the healthcare needs and quality of life of members of the armed forces, who are deployed, including their family members. Our proposed Phase 2 clinical trial in subjects receiving care at the William S. Middleton Memorial Veterans Hospital, Madison, WI will evaluate the use of a biotherapeutic agent, Lactobacillus rhamnosus HN001, to reduce colonization by antimicrobial-resistant bacteria and thereby prevent serious infections. We have two hypotheses: (1) The probiotic L. rhamnosus HN001, when compared with placebo, will reduce S. aureus nasal colonization by 50% when taken for four weeks, by increasing phagocytic activity of white cells (2) The probiotic L. rhamnosus HN001, when compared with placebo, will reduce S. aureus gastrointestinal colonization by 50% when taken for four weeks. To investigate these hypotheses, we are proposing the following specific aims: Primary Specific Aims 1. To determine the effect of 4 weeks of oral L. rhamnosus HN001 therapy on nasal and gastrointestinal colonization of S. aureus when compared with placebo. 2. To determine the effect of 4 weeks of oral L. rhamnosus HN001 therapy on phagocytic functioning of polymorphonuclear (PMN) and monocyte cells. Secondary Exploratory Specific Aim 1. To determine the effect of 4 weeks of oral L. rhamnosus HN001 therapy on S. aureus infections. Our study population includes patients seeking care in the outpatient or inpatient setting at the William S. Middleton Memorial Veterans Hospital, Madison WI who are colonized with S. aureus in the nose, gastrointestinal site, or both. Potential subjects will be identified by reviewing infection control lists of patients known to be colonized with S. aureus, including the resistant form of S. aureus, methicillin-resistant S. aureus (MRSA). We will identify additional subjects by collecting nasal swabs and perirectal swabs or stool specimens from patients at high risk of S. aureus colonization. Subjects who found to be colonized by S. aureus will be randomized to probiotic or placebo, which they will take once daily for 4 weeks. Stool specimens will be collected once weekly for 4 weeks. Nasal specimens will be collected at baseline and 4 weeks. The primary outcome is colonization by S. aureus in the nose, gastrointestinal tract, or both at the end of 4 weeks of treatment. Secondary outcomes include clinical infections by S. aureus, as defined by criteria from the Centers for Disease Control, during the 4 weeks of probiotic or placebo treatment. Data collection will occur by electronic chart review. Adherence will be encouraged by weekly phone calls. If found to be efficacious, probiotics represent an easily implementable, safe, and well-tolerated intervention that is suitable for use in a field environment and requires no special conditions for it to be used.